Multiple sclerosis is a disease of the central nervous system with variable neurologic deficits due to demyelination in the brain and spinal cord. The course of the disease is variable, in some patients multiple sclerosis is chronic and progressive. Although the etiology is not precisely understood, there is convincing evidence that the disease is of an autoimmune nature. Defective and abnormal immune responses have been observed. Current evidence indicates that the defective immune response causes destruction of central nervous system myelin by the autoreactive (cytotoxic lymphocyte) cells. The damage is initiated in two stages: In the first stage, T4 (helper-inducer) cells stimulate the T8 CTL cells to proliferate; and in the second stage, the T4 and the T8 cells are believed to be a direct cause of primary lesions. During this process the T4 cells recruit macrophages which may also cause direct cell damage. It is thus believed that the T4 cells mediate this autoimmune process. Finally, there is evidence that a basic defect in the T4 cell is a failure to induce proliferation of another subset of T8 suppressor cells which would normally inhibit the above progression. The defective T4 suppressor-inducer cells thus fail to perform the normal inhibitory function.
As a result of these immunological defects, attempts have been made to interrupt the course of the disease with immunosuppression. See: (1) "Intensive Immunosuppression in Progressive Multiple Sclerosis," New England Journal of Medicine, Vol. 308, No. 4, Jan. 1983, S. L. Hauser, et al; (2) "Plasma Exchange and Lymphocytapheresis in Multiple Sclerosis," Int J Artif Organs, 7:39-42, 1984, P. Hocker, et al; and (3) "Long-Term Lymphocytapheresis Therapy in Multiple Sclerosis," Eur Neurol, 25:225-236, 1986, E. Maida, et al.
In reference 1, 58 patients were divided into three groups. All patients received ACTH R.sub.X and one of the three groups received only ACTH. The second group received high-dose cyclophosphamide and the third group was treated with plasma exchange and low-dose cyclophosphamide administered orally. It was discovered that high-dose cyclophosphamide plus ACTH was the most effective in halting disease progression. However, in this study there was no lymphocytapheresis. Patients were treated with low-dose (2 mg/Kg/day unless the WBC was less than 4000 .mu.l) intravenous cyclophosphamide and ACTH for producing hydrocortisone by stimulating the adrenal gland. In the plasmapheresis group, the cyclophosphomide was administered orally.
In reference 2, treatment with azathioprine and prednisone was combined with plasmapheresis, performed either four times in two weeks or two to three times in one week. In patients with persistent disease of over five years duration, there was an improvement in 50% to 70% of the cases. In this protocol there was no maintenance lymphocytapheresis, and the number of lymphocytes removed and the numbers of peripheral blood lymphocytes were not monitored.
In reference 3, a long-term therapy was administered without an intense induction phase. In this protocol, the number of lymphocytes removed was determined but the PBL counts were not monitored as the measure of effective therapy. Improvement was obtained in 3 of 9 patients, and a decrease in the relapse rate in 6 of 9 patients was observed. There were no relapses in 7 of 9 patients while on LCP. In this treatment lymphocytapheresis was not combined with any other therapy. Two-thirds of the patients remained unchanged but suffered exacerbations less often.